Abstract: Objective To identify the differentially expressed genes in systemic lupus erythematosus (SLE) by comparing the gene expression profiles of peripheral leukocytes between SLE patients and healthy controls. Methods The total RNA was extracted from 5 ml peripheral blood of normal subjects and SLE patients, and reversely transcribed in cDNA templates to synthesize cDNA probes labeled for hybridization with the microarray. Results Totally 89 over- or under-expressed genes were identified in 9 SLE patients as compared with the controls. These genes included genes associated with cytokines and their receptors, immunity, cell signal transduction, protein transcription and synthesis, ion channel and transporters, cell apoptosis, DNA and RNA processing, and extracellular matrix etc. Clustering analysis showed that in spite of the individual diversity of the SLE patients, their gene expression profiles were strikingly similar. Conclusion The differentially expressed genes screened with oligonucleotide DNA microarray technique may provide clues for exploring the pathogenesis and progression of SLE, and for identification of potential molecular markers for diagnosis and development of therapeutic drugs.